Summary of work: The Department of Nuclear Medicine, in conjunction with the National Cancer Institute and the Department of Radiology, performs clinical research in the use of imaging in oncology. In particular, they are studying the use of Positron Emission Tomographic (PET) images, in conjunction with CT and MR images, to evaluate the effects of therapy on tumors. Several therapeutic agents are being studied, among them various anti-angiogenesis therapies. The PET scanners are used to measure glucose metabolism, blood flow and blood volume in tumors over the course of therapy. CT scans are used to determine tumor morphology, and MR imaging is used to determine both morphology and parameters related to tumor perfusion. This research is geared toward developing, implementing and testing methods to better quantify the data obtained from the images, and to determine if these methods are efficacious for the monitoring of tumor therapy. These methods involve both determination of tumor morphology, as well as the optimal determination of functional parameters such as blood flow, metabolism, and blood volume. The overall goal is the development of a clinically useful methodology for determining tumor response to therapy at an earlier phase of therapy than is currently possible. Such a methodology could permit optimal adjustment of the course of therapy while the therapy was still proceeding, potentially improving both tumor response and patient morbidity. Several areas of investigation are being pursued toward achieving this goal. Some of the principal ones are listed below. 1. Development of new reconstruction techniques which will improve noise properties of the image sets. This noise reduction will both improve the ability of the physician to visually interpret the images, as well as improve the noise in quantitative parameters derived from the images. This work has now been published in the Journal of Nuclear Medicine (Noise Reduction in Oncology FDG PET Images by Iterative Reconstruction: A Quantitative Assessment. J Nucl. Med. 42:1316-1323, Sept. 2001). As a result of this work, all reconstructions in oncology are now performed with the new iterative reconstruction method. 2. Assessment of the physiologic models employed for blood flow measurement, using O-15 water. Several models are being analyzed, especially in regards to their utility in producing functional flow images. In addition, the results of these PET flow models are being compared to similar data obtained from Gd-DTPA dynamic MR images. The variability and reproducibility of each of the methods is also being determined, using replicate measurements. The first data from these studies has recently been published (Parametric Images of Blood Flow in Oncology PET Studies Using 15-O water, J Nucl Med 2000;41:1784-1792 and Measuring Tumor Blood Flow with H2O15: Practical Considerations. Nuc. Med. Biol. 27:671-676 (2000). Further work will focus on better models to account for tumor heterogeneity. 3. Methods for making accurate, non invasive measurement of the arterial input function are being assessed. These methods compare LV cavity and aorta derived arterial input functions with actual arterial sampling. Several schemes are being explored to correct for partial volume and spill in/out effects. The results of this work are being prepared for publication (the fellow performing the work has recently finished his fellowship). 4. Methods for using 3D region growing to more accurately assess tumor volume, metabolic volume and perfused tumor volume are being explored. These methods will be employed to make objective assessments of the various physiologic parameters (e.g. FDG "uptake"), and ROC analysis used to determine which of these quantitative indices are best for detecting disease, and to determine if quantitative measures are better than subjective visual assessment. 5. The results of the above 4 methodologies have recently been applied inpractise to the first completed protocol (Thalidomide for Prostate Metastases). The clinical results of this analysis are being submitted for publication.